{"protocolSection":{"identificationModule":{"nctId":"NCT00602537","orgStudyIdInfo":{"id":"R01MH060353-02","type":"NIH","link":"https://reporter.nih.gov/quickSearch/R01MH060353-02"},"secondaryIdInfos":[{"id":"R01MH060353-02","type":"NIH","link":"https://reporter.nih.gov/quickSearch/R01MH060353-02"},{"id":"2R01MH060353-06A2","type":"NIH","link":"https://reporter.nih.gov/quickSearch/2R01MH060353-06A2"}],"organization":{"fullName":"University of Pennsylvania","class":"OTHER"},"briefTitle":"Antidepressant Therapy in Treating Bipolar Type II Major Depression","officialTitle":"Treatment of Bipolar Type II Major Depression"},"statusModule":{"statusVerifiedDate":"2017-04","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2007-12"},"primaryCompletionDateStruct":{"date":"2013-06","type":"ACTUAL"},"completionDateStruct":{"date":"2013-06","type":"ACTUAL"},"studyFirstSubmitDate":"2008-01-15","studyFirstSubmitQcDate":"2008-01-15","studyFirstPostDateStruct":{"date":"2008-01-28","type":"ESTIMATED"},"resultsFirstSubmitDate":"2016-11-10","resultsFirstSubmitQcDate":"2017-04-21","resultsFirstPostDateStruct":{"date":"2017-04-25","type":"ACTUAL"},"lastUpdateSubmitDate":"2017-04-21","lastUpdatePostDateStruct":{"date":"2017-04-25","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"University of Pennsylvania","class":"OTHER"},"collaborators":[{"name":"National Institute of Mental Health (NIMH)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"This study will compare the safety and effectiveness of antidepressant therapy versus mood stabilizing therapy in treating people with bipolar type II major depression.","detailedDescription":"Bipolar type II (BP II) depression affects 2.5% of the U.S. adult population. People with BP II disorder do not experience the manic episodes that are characteristic of BP I disorder, but rather they experience more modest mood swings with a greater number of major depressive episodes (MDEs). These MDEs are associated with high rates of disease and death. The treatment of BP II depression remains a challenge for clinicians. Mood stabilizer (MS) monotherapy is the current recommended treatment for BD II MDE, but there is reason to believe that antidepressant drug (AD) monotherapy could also be an effective treatment. However, concerns over AD-induced manic switch episodes have limited the use of this treatment option. Preliminary studies using the ADs fluoxetine or venlafaxine have shown success in treating and lowering the manic switch rate of those with BP II MDE. This study will compare the safety and effectiveness of AD monotherapy versus MS monotherapy in treating people with BP II major depression.\n\nParticipation in this double-blind study will last up to 9 months. After screening, which includes a medical and psychiatric history review, a physical exam, an electrocardiogram (EKG) test, clinical laboratory tests, a urine-based drug test, and a pregnancy test if applicable, participants will be randomly placed into one of two treatment groups. Participants in the AD monotherapy group will be treated with venlafaxine, and participants in the MS monotherapy group will be treated with lithium. During the first 12 weeks, there will be a total of nine study visits lasting between 45 and 60 minutes. In these visits, participants will receive their study drug and will undergo various assessments, including a review of medication history and side effects, vital sign measurements, and questionnaires about depression and daily functioning. Blood samples will be taken at most visits.\n\nParticipants who respond well during the initial 12 weeks of therapy with either drug will have the option to continue treatment for 6 additional months. During this time, participants will continue their assigned treatment and will attend five monthly study visits that will repeat previous assessments and procedures.\n\nFor information on a related study, please follow this link:\n\nhttp://clinicaltrials.gov/show/NCT00044616"},"conditionsModule":{"conditions":["Bipolar Disorder","Depression"],"keywords":["Bipolar Type II Disorder","Hypomania","Antidepressant","Mood Stabilizer","Venlafaxine","Lithium Carbonate","Major Depressive Episode","Hypomanic Episodes","Prevention of Depression Relapse"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":140,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"I","type":"EXPERIMENTAL","description":"Antidepressant therapy","interventionNames":["Drug: Venlafaxine"]},{"label":"II","type":"ACTIVE_COMPARATOR","description":"Mood stabilizer therapy","interventionNames":["Drug: Lithium Carbonate"]}],"interventions":[{"type":"DRUG","name":"Venlafaxine","description":"75 to 375 mg","armGroupLabels":["I"]},{"type":"DRUG","name":"Lithium Carbonate","description":"300 to 2400 mg","armGroupLabels":["II"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Depressive Relapse","description":"These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered \"depressive relapse\" if relapsed by any of these times.","timeFrame":"Weeks 16, 20, 24, 30, 36"}],"secondaryOutcomes":[{"measure":"Treatment-Emergent Mood Symptoms","description":"These subjects must be responders.","timeFrame":"Measured at Weeks 12 and 36"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Meets DSM-IV criteria for Axis I bipolar II disorder\n* Meets DSM-IV criteria for Axis I major depressive episode\n* Score of 16 on 17-item HAM-D rating scale\n* Not taking monoamine oxidase inhibitors (MAOI) for more than 2 weeks prior to study entry\n* Willing to use an effective form of birth control throughout the study\n\nExclusion Criteria:\n\n* History of mania\n* Current primary Axis I diagnosis other than bipolar II disorder\n* Alcohol or drug dependence within 3 months prior to study entry\n* Contraindication to treatment with venlafaxine or lithium\n* Unstable medical condition (e.g., thyroid disease, hypertension, or angina pectoris)\n* Pregnant or breastfeeding\n* Experiencing suicidal thoughts\n* Requires hospitalization\n* Requires concurrent neuroleptic or MS therapy\n* Requires concurrent AD therapy\n* Current psychotic features\n* Inadequate trial of therapy at the time of initial screening visit\n* History of intolerance to either venlafaxine or lithium\n* Unlikely to participate in a 36-week trial\n* Presence of apparent secondary gain","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Robert J. DeRubeis, PhD","affiliation":"University of Pennsylvania","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Depression Research Unit - University of Pennsylvania","city":"Philadelphia","state":"Pennsylvania","zip":"19104-3309","country":"United States","geoPoint":{"lat":39.95238,"lon":-75.16362}}]},"referencesModule":{"references":[{"pmid":"29149756","type":"DERIVED","citation":"Lorenzo-Luaces L, Amsterdam JD, DeRubeis RJ. Residual anxiety may be associated with depressive relapse during continuation therapy of bipolar II depression. J Affect Disord. 2018 Feb;227:379-383. doi: 10.1016/j.jad.2017.11.028. Epub 2017 Nov 8."},{"pmid":"29136600","type":"DERIVED","citation":"Lorenzo-Luaces L, Amsterdam JD. Effects of venlafaxine versus lithium monotherapy on quality of life in bipolar II major depressive disorder: Findings from a double-blind randomized controlled trial. Psychiatry Res. 2018 Jan;259:455-459. doi: 10.1016/j.psychres.2017.11.025. Epub 2017 Nov 8."},{"pmid":"28160351","type":"DERIVED","citation":"Amsterdam JD, Lorenzo-Luaces L, DeRubeis RJ. Comparison of treatment outcome using two definitions of rapid cycling in subjects with bipolar II disorder. Bipolar Disord. 2017 Feb;19(1):6-12. doi: 10.1111/bdi.12462. Epub 2017 Feb 3."},{"pmid":"27805299","type":"DERIVED","citation":"Amsterdam JD, Lorenzo-Luaces L, DeRubeis RJ. Step-wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression. Bipolar Disord. 2016 Nov;18(7):563-570. doi: 10.1111/bdi.12442. Epub 2016 Nov 2."},{"pmid":"26892848","type":"DERIVED","citation":"Amsterdam JD, Lorenzo-Luaces L, Soeller I, Li SQ, Mao JJ, DeRubeis RJ. Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate. Br J Psychiatry. 2016 Apr;208(4):359-65. doi: 10.1192/bjp.bp.115.169375. Epub 2016 Feb 18."},{"pmid":"26803764","type":"DERIVED","citation":"Lorenzo-Luaces L, Amsterdam JD, Soeller I, DeRubeis RJ. Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk. Acta Psychiatr Scand. 2016 Jun;133(6):459-69. doi: 10.1111/acps.12557. Epub 2016 Jan 24."},{"pmid":"26143402","type":"DERIVED","citation":"Amsterdam JD, Lorenzo-Luaces L, Soeller I, Li SQ, Mao JJ, DeRubeis RJ. Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study. J Affect Disord. 2015 Oct 1;185:31-7. doi: 10.1016/j.jad.2015.05.070. Epub 2015 Jun 26."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Antidepressant Therapy","description":"Venlafaxine: 75 to 375 mg"},{"id":"FG001","title":"Mood Stabilizer Therapy","description":"Lithium Carbonate: 300 to 2400 mg"}],"periods":[{"title":"12 Week Double Blind Comparison","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"65"},{"groupId":"FG001","numSubjects":"64"}]},{"type":"Responded","achievements":[{"groupId":"FG000","numSubjects":"44"},{"groupId":"FG001","numSubjects":"22"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"42"},{"groupId":"FG001","numSubjects":"17"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"23"},{"groupId":"FG001","numSubjects":"47"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"Lack of Efficacy","reasons":[{"groupId":"FG000","numSubjects":"13"},{"groupId":"FG001","numSubjects":"23"}]},{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"5"},{"groupId":"FG001","numSubjects":"6"}]},{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"13"}]}]},{"title":"Follow Up Study Comparison","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"42"},{"groupId":"FG001","numSubjects":"17"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"31"},{"groupId":"FG001","numSubjects":"14"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"11"},{"groupId":"FG001","numSubjects":"3"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"8"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"2"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Antidepressant Therapy","description":"Venlafaxine: 75 to 375 mg"},{"id":"BG001","title":"Mood Stabilizer Therapy","description":"Lithium Carbonate: 300 to 2400 mg"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"42"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"59"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"41.8","spread":"11.4"},{"groupId":"BG001","value":"43.1","spread":"15.2"},{"groupId":"BG002","value":"42.2","spread":"12.5"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"24"},{"groupId":"BG001","value":"8"},{"groupId":"BG002","value":"32"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"18"},{"groupId":"BG001","value":"9"},{"groupId":"BG002","value":"27"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"1"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"9"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"37"},{"groupId":"BG001","value":"12"},{"groupId":"BG002","value":"49"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Inter-episode recovery","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"16"}]}]}]},{"title":"Age 1st major depressive episode","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"19.0","spread":"7.7"},{"groupId":"BG001","value":"17.4","spread":"5.4"},{"groupId":"BG002","value":"18.5","spread":"7.1"}]}]}]},{"title":"Age 1st hypomanic episode","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"20.7","spread":"7.6"},{"groupId":"BG001","value":"16.2","spread":"10.0"},{"groupId":"BG002","value":"19.4","spread":"8.5"}]}]}]},{"title":"Number of lifetime major depressive episodes","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"Episodes","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"28.4","spread":"50.4"},{"groupId":"BG001","value":"33.3","spread":"49.7"},{"groupId":"BG002","value":"29.9","spread":"11.0"}]}]}]},{"title":"Number of lifetime hypomanic episodes","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"Episodes","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"45.8","spread":"66.4"},{"groupId":"BG001","value":"32.2","spread":"47.3"},{"groupId":"BG002","value":"41.9","spread":"61.4"}]}]}]},{"title":"Baseline HRSD score","description":"This scale refers to the 17-item Hamilton Rating Scale for Depression and measures patient depressive severity. The scale ranges from 0 to 52, with higher scores representing worse outcome.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"19.4","spread":"3.6"},{"groupId":"BG001","value":"18.8","spread":"3.3"},{"groupId":"BG002","value":"19.2","spread":"3.5"}]}]}]},{"title":"Baseline YMRS score","description":"This scale refers to the Young Mania Rating Scale and measures manic symptoms. The scale ranges from a minimum score of 0 to a maximum score of 60, with higher scores representing worse outcome.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"0.8","spread":"1.7"},{"groupId":"BG001","value":"0.6","spread":"1.4"},{"groupId":"BG002","value":"0.8","spread":"1.6"}]}]}]},{"title":"Duration major depressive episode","paramType":"MEDIAN","dispersionType":"FULL_RANGE","unitOfMeasure":"months","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"4.5","lowerLimit":".75","upperLimit":"60"},{"groupId":"BG001","value":"4.0","lowerLimit":"0","upperLimit":"396"},{"groupId":"BG002","value":"4","lowerLimit":"0","upperLimit":"60"}]}]}]},{"title":"Baseline HRSD Score for Follow-Up study","description":"This scale refers to the 17-item Hamilton Rating Scale for Depression and measures patient depressive severity. The scale ranges from 0 to 52, with higher scores representing worse outcome.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"4.3","spread":"2.8"},{"groupId":"BG001","value":"4.4","spread":"3.4"},{"groupId":"BG002","value":"4.3","spread":"2.9"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Depressive Relapse","description":"These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered \"depressive relapse\" if relapsed by any of these times.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Weeks 16, 20, 24, 30, 36","groups":[{"id":"OG000","title":"Antidepressant Therapy","description":"Venlafaxine: 75 to 375 mg"},{"id":"OG001","title":"Mood Stabilizer Therapy","description":"Lithium Carbonate: 300 to 2400 mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"40"},{"groupId":"OG001","value":"15"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"4"}]}]}]},{"type":"SECONDARY","title":"Treatment-Emergent Mood Symptoms","description":"These subjects must be responders.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Measured at Weeks 12 and 36","groups":[{"id":"OG000","title":"Antidepressant Therapy","description":"Venlafaxine: 75 to 375 mg"},{"id":"OG001","title":"Mood Stabilizer Therapy","description":"Lithium Carbonate: 300 to 2400 mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"40"},{"groupId":"OG001","value":"15"}]}],"classes":[{"title":"Any depression","categories":[{"measurements":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"11"}]}]},{"title":"Any subsyndromal hypomania","categories":[{"measurements":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","eventGroups":[{"id":"EG000","title":"Antidepressant Therapy","description":"Venlafaxine: 75 to 375 mg","seriousNumAffected":0,"seriousNumAtRisk":65,"otherNumAffected":0,"otherNumAtRisk":65},{"id":"EG001","title":"Mood Stabilizer Therapy","description":"Lithium Carbonate: 300 to 2400 mg","seriousNumAffected":0,"seriousNumAtRisk":64,"otherNumAffected":0,"otherNumAtRisk":64}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Dr. Jay Amsterdam","organization":"University of Pennsylvania","email":"jamsterd@mail.med.upenn.edu","phone":"(215) 662-3462"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D001714","term":"Bipolar Disorder"},{"id":"D003863","term":"Depression"},{"id":"D000087122","term":"Mania"}],"ancestors":[{"id":"D000068105","term":"Bipolar and Related Disorders"},{"id":"D019964","term":"Mood Disorders"},{"id":"D001523","term":"Mental Disorders"},{"id":"D001526","term":"Behavioral Symptoms"},{"id":"D001519","term":"Behavior"},{"id":"D019954","term":"Neurobehavioral Manifestations"},{"id":"D009461","term":"Neurologic Manifestations"},{"id":"D009422","term":"Nervous System Diseases"},{"id":"D012816","term":"Signs and Symptoms"},{"id":"D013568","term":"Pathological Conditions, Signs and Symptoms"}]},"interventionBrowseModule":{"meshes":[{"id":"D000069470","term":"Venlafaxine Hydrochloride"},{"id":"D016651","term":"Lithium Carbonate"}],"ancestors":[{"id":"D003511","term":"Cyclohexanols"},{"id":"D000441","term":"Hexanols"},{"id":"D005233","term":"Fatty Alcohols"},{"id":"D000438","term":"Alcohols"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D010627","term":"Phenethylamines"},{"id":"D005021","term":"Ethylamines"},{"id":"D000588","term":"Amines"},{"id":"D003510","term":"Cyclohexanes"},{"id":"D003516","term":"Cycloparaffins"},{"id":"D006840","term":"Hydrocarbons, Alicyclic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"},{"id":"D008055","term":"Lipids"},{"id":"D002254","term":"Carbonates"},{"id":"D000468","term":"Alkalies"},{"id":"D007287","term":"Inorganic Chemicals"},{"id":"D002255","term":"Carbonic Acid"},{"id":"D017554","term":"Carbon Compounds, Inorganic"},{"id":"D018020","term":"Lithium Compounds"}]}},"hasResults":true}